EP0732112A1 - Implantable infusion pump - Google Patents

Abstract

The object is an implantable infusion pump for the metered delivery of medication into the human body, comprising a pump chamber which is formed by a lower chamber part and an upper chamber part connected to it, the pump chamber being separated into two partial chambers by a gas-impermeable flexible partition, the first partial chamber from the upper chamber part and the flexible partition is limited and is designed as a storage for medical solutions, the chamber upper part has a refill opening which is sealed by at least one pierceable septum and the storage for medical solutions is connected to an outlet catheter via an outlet opening and optionally an outlet reducing device, and the second sub-chamber is delimited by the lower chamber part and the flexible dividing wall and is designed as a pressure chamber for receiving hexafluorobutane, in particular 1,1,1,4,4,4-hexafluorobutane used as a blowing agent. The implantable infusion pump according to the invention is unproblematic in terms of safety technology, has a delivery rate that is independent of the medication volume, a relatively low temperature gradient, is safe and easy to use, medication-compatible, simple and inexpensive to manufacture and consists of body-compatible material and compatible materials.

Description

The present invention relates to an implantable infusion pump for the metered delivery of medication into the human body according to the preamble of patent claim 1.

Implantable infusion pumps are already known. From DE 39 15 251 A1 an implantable infusion pump is known which has a pump chamber which is formed by a bowl-shaped lower chamber part and an upper chamber part connected to it. The pump chamber is separated into two sub-chambers by a flexible membrane. A first partial chamber is delimited by the upper chamber part and the membrane and is designed as a medicament store. The top part of the chamber contains a refill opening which is sealed with a pierceable septum. The septum is clamped between a septa holder connected to the upper chamber part and the upper chamber part. The medicament store is connected to an outlet catheter via an outlet opening and optionally an outlet reducing device. A second sub-chamber is delimited by the lower part of the chamber and the membrane and is provided as a pressure chamber for receiving a propellant that expands at body temperature.

Infusion pumps with a similar structure are also known from DE 26 04 113 A1, DE 21 24 062 B2 and DE 40 38 049 A1. Another infusion pump is described in DE 44 32 991 A1, to which express reference is made here for the purposes of disclosure.

The pump components in these infusion pumps consist of body-compatible metal alloys or plastics that are connected to one another by welded connections or residual connections.

Implantable infusion pumps are arranged in a subcutaneous pocket in the region of the patient's abdomen, the refill opening closed with the septum being palpable under the patient's skin. The medication store is filled by pricking a syringe with an appropriate cannula through the patient's skin and through the septum. The medication flows through the cannula into the medication store due to the syringe pressure.

Implantable infusion pumps are used for continuous medication (constant dose) over long periods of time in patients who would otherwise only be injected with the medication, e.g. of morphine, heparins and the like can be treated several times a day. The pumps have the advantage over the usual injection that the administered dose no longer has to be overdosed to such an extent that, despite the breakdown of the medicament by the next administration point, the dose does not fall below a certain minimum, but instead achieves a uniform and substantially reduced supply of the medicament can be. Such infusion pumps have to meet high safety requirements, especially when painkillers are administered. Any overdosing or underdosing must be avoided. Depending on the medication administered, an overdose can lead to a high health risk, in particular with painkillers, it can even be fatal.

The operation of an implantable infusion pump is essentially such that the propellant contained in the pump, the boiling point of which is below body temperature, partially evaporates in the patient's body after implantation of the pump and via the partition, such as a flexible membrane or a bellows, exerts pressure on the medication in the medication store, whereupon the medication flows to the target organ via a reduction system and a catheter. The medication room shrinks while increasing the propellant gas space. The increase in volume of the propellant gas space is absorbed by a further evaporation of the propellant and is isobaric at a constant temperature as long as the propellant is in a two-phase system and no foreign gases exist in the propellant space. Isobaric pressure development is necessary for the systems to maintain a constant delivery rate.

The propellants previously used in the implantable infusion pumps do not meet the requirements placed on them. They pose numerous problems.

In the infusion pump known from DE 40 38 049 A1, 1,2-dichlorotetrafluoroethane is used as the blowing agent. This blowing agent develops a pressure of over 2.5 bar above atmospheric pressure at body temperature (about 37 ° C). This pressure must be overcome when the medication is refilled, which places high demands on the doctor entrusted with the refilling and puts a strain on the patient. In addition, this propellant is a safety concern because the walls of the implant are subjected to higher loads. A lower safety-related load on the walls of the implant is achieved when using Frigen 11. Frigen 11 is, however, like 1,2-dichlorotetrafluoroethane, a chlorofluorocarbon (CFC), whose use has to be avoided due to its adverse effects on the environment (including ozone depletion). Frigen 11 develops a pressure of only about 0.6 bar above atmospheric pressure at body temperature and would be preferable to using 1,2-dichlorotetrafluoroethane for safety reasons. With the 1,2-dichlorotetrafluoroethane used as a blowing agent according to DE 40 38 049 A1, the delivery rate of the infusion pump is less of temperature changes (for example in the case of a patient's fever) and changes in the counterpressure at the end of the catheter (for example Changes in blood pressure, changes in air pressure, for example when traveling by air or staying in the mountains) than when using, for example, Frigen 11. For the safety reasons mentioned, Frigen 11 would still be preferable to 1,2-dichlorotetrafluoroethane.

Further problems arise with previously used blowing agents from their relative incompatibility with the materials surrounding them, such as metals and plastics, in particular with plastics.

The object of the present invention is therefore to provide an implantable infusion pump which does not contain CFCs as a propellant, is not problematic from a safety point of view, in which a maximum pressure of 2 bar is not exceeded when the temperature rises as a result of a patient's fever (42 ° C.), the delivery rate being independent of the medicament volume and there is a relatively low temperature gradient, which is safe and easy to use, is compatible with medication, consists of body-compatible material and compatible materials and is simple and inexpensive to produce.

This object is achieved in an implantable infusion pump of the type mentioned at the outset in that the propellant according to the invention is hexafluorobutane.

Preferably the blowing agent is 1,1,1,4,4,4-hexafluorobutane.

The blowing agent used according to the invention has a boiling point of 23 ° C. It is non-toxic and inert to the materials used in the infusion pump, especially plastics. With regard to its pressure-temperature behavior, the propellant gas used according to the invention is quite close to Frigen 11. At body temperature (about 37 ° C.), the propellant develops a pressure of about 670 mbar above atmospheric pressure. The attached FIG. 1 shows a temperature / pressure curve of the one preferably used according to the invention It represents a relatively low temperature gradient for the blowing agent used according to the invention. The pressure increase per temperature change of 1 ° C is a maximum of 70 mbar and is in particular in the range of 55-67 mbar. With regard to these properties, the blowing agent used according to the invention can also be regarded as safe in terms of safety. There is therefore no heavy load on the housing of the infusion pump according to the invention. Furthermore, the refilling of the medication does not require high syringe forces by the doctor entrusted with it and the stress on the patient is reduced.

The pressure chamber can be filled with the propellant in any suitable manner after the existing air has been removed from the pressure chamber (e.g. by suction). E.g. a microcapillary can be inserted through the sealing surface, through which the propellant is filled into the pressure chamber. After filling with the propellant, the capillary can be cast or pulled out. The amount of propellant filled is small and can be, for example, 2 ml, while the internal volume of the pressure chamber e.g. can be about 40 ml.

The infusion pumps can be designed in any suitable form and made of any suitable body-compatible material, such as metal or plastic. Plastics are preferably used, with hard plastics such as polysulfones (including polyether sulfones), polyamides and polycarbonates, in particular polysulfones, being preferred. The use of plastic infusion pumps brings considerable advantages. In addition to the lower weight compared to metal infusion pumps, plastic infusion pumps create the prerequisites for the simultaneous use of certain therapeutic or diagnostic methods, such as thermography or NMR.

In particular, the infusion pumps are designed as they are described in DE 44 32 991 A1 and / or in the patent application filed at the same time with the present patent application with the file number P 195 09 634.7-35 with the title "implantable infusion pump" (our symbol FR2665) .

The infusion pump according to the invention is for the continuous metered delivery of medicaments, e.g. Heparin, artificial pancreatic insulin, chemotherapy drugs, pain relievers such as morphine, muscle relaxants such as baclofen and the like are suitable.

The following examples serve to further explain the present invention.

example 1

FIG. 2 shows a vertical section through an schematically illustrated implantable infusion pump according to the invention. The infusion pump 1 is a disk-shaped, rotationally symmetrical body made of hard plastic with a pump chamber, which is formed by a lower chamber part 2 and an upper chamber part 3 and by the flexible gas-impermeable partition 6 in two partial chambers 7 and 8 is separated. The first sub-chamber 7 serves as a medicament storage and the second sub-chamber 8 serves as a pressure chamber for receiving the 1,1,1,4,4,4-hexafluorobutane used as a blowing agent. The refill opening 12 is covered by a pierceable central septum 13 and has a refill space below the central septum 13 with a fixed plate as a needle stop and through openings to the medicament store 7.

The flexible gas impermeable partition 6 is a commonly used flexible membrane.

• a) Folie aus Polyethylenterphthalat, Dicke 100 µm
• b) Folie aus Polychlortrifluorethylen, Dicke 127 µm
• c) Aluminiumverbundfolie aus
  • i) Polyethylenterphthalatfolie, Dicke 12 µm
  • ii) Aluminiumfolie, Dicke 12 µm
  • iii) Polyethylenfolie, Dicke 70 µm.

According to a further embodiment, the flexible gas-impermeable partition 6 is curved in accordance with the contour of the inner shape of the upper chamber part 3 (and corresponding to the lower chamber part 2), which was achieved by deep drawing. This partition is free of tension. It consists of a film system which, viewed from the medication store 7, is composed as follows:

• a) film of polyethylene terephthalate, thickness 100 microns
• b) Polychlorotrifluoroethylene film, thickness 127 µm
• c) aluminum composite film
  • i) polyethylene terephthalate film, thickness 12 microns
  • ii) aluminum foil, thickness 12 µm
  • iii) polyethylene film, thickness 70 microns.

The foils of the aluminum composite foil are glued together using a polyurethane adhesive. The foils a) and b) are connected to one another and to the aluminum composite foil only in the edge region along the entire circumference. The partition 6 is clamped or pressed in with its outer edge region along its circumference between the edge regions of the upper chamber part 3 and the lower chamber part 2.

The 1,1,1,4,4,4-hexafluorobutane used as the blowing agent was brought into the pressure chamber in such a way that a microcapillary was introduced through the sealing surface in the edge region, the air was removed from the pressure chamber and the blowing agent was introduced into the pressure chamber through the microcapillary filled in. The amount filled was about 2 ml.

The internal volume of the pressure chamber 8 is approximately 40 ml, the medicament store 7 can hold approximately 30 ml of the medical solution.

Example 2

FIG. 3 shows a vertical section through a specially designed infusion pump for the metered delivery of medication into the human body.

The infusion pump 1 is a disk-shaped, rotationally symmetrical body made of polysulfone, which has a housing which is composed of a bowl-shaped lower chamber part 2, a bowl-shaped chamber upper part 3 with an opposite curvature, a cap part 4 and a septa holder 5. The interior is divided by a curved partition 6 and a likewise curved aluminum composite film P into a first partial chamber, which serves as a medicament storage 7, and a second partial chamber, which acts as a pressure chamber 8 for receiving the 1,1,1,4,4, 4-hexafluorobutane is used. The pressure chamber 8 is formed by edge welding or gluing the partition 6 and the aluminum composite film P and is shaped like a pill.

At the upper inner edge region of the lower chamber part 2, an annular groove is formed, into which a circumferential associated edge 10 of the upper chamber part 3 is latched together with an O-ring 11 and an edge 36, which is formed from the partition wall 6 and the aluminum composite film P, in a snap connection and is kept tight.

A refill opening 12 is tightly covered by a disk-shaped and pierceable central septum 13, the refill opening 12 having a refill space under the central septum 13 with a fixed plate as a needle stop and through openings to the medicament store 7.

Furthermore, a concentric annular chamber 14 is formed on the upper side of the upper chamber part 3, which is tightly covered by an annular septum 15.

A concentric annular groove 16 is formed between the annular chamber 14 and the refill opening 12, on the inner and outer side wall of which a circumferential locking groove 17, 18 is provided. The ring-shaped septa holder 5 engages with its inner edge over the edge of the disc-shaped central septum 13 and with its outer edge the ring-inner edge of the ring septum 15. In addition, the septa holder 5 engages in the ring groove 16 with ring webs 19, 20 lying next to one another, the locking lugs 21, 22 engage on the ring webs 19, 20 in the locking grooves 17, 18.

The outer edge of the ring septum 15 is covered in a step-like arrangement by a correspondingly shaped edge area of the union part 4 and tightly clamped against the upper chamber part 3. For this purpose, a latching connection between the union part 4 and the upper chamber part 3 is provided in this edge region of the union part 4, which consists of a circumferential latching groove 23 on the union part 4 and a circumferential latching lug 24 on the chamber upper part 3.

A further annular groove 25 is formed on the lateral outer edge region of the lower chamber part 2, into which a circumferential locking lug 26 engages together with an inserted O-ring 27. The locking lug 26 represents the lower edge of the union part 4, this engaging over the side region of the chamber upper part 3 and the outer lateral edge region of the chamber lower part 2 in a bell-shaped manner. The coupling part 4 is supported (with a large pressure load) on the upper chamber part 3 via the locking lug arrangement 24 and over the ring septum 15 towards the lower chamber part 2.

Between the outer wall area of the upper chamber part 3 and an inner wall area of the coupling part 4, an annular space 28 for receiving an outlet reducing device 29 (shown here schematically as a section through a capillary) and an outlet catheter 30 are formed.

The connection 31, formed from the annular groove 9, the edge 10 and the O-ring 11, the connection 32, formed from the locking groove 23 and the locking lug 24, and the connection 33, consisting of the locking groove 18 and the locking lugs 22, provide main connections represent, which support the occurring internal pressure loads under normal operational load essentially.

The connection 34, consisting of the annular groove 25, the locking lug 26 and the O-ring 27, as well as the connection 35, consisting of the locking groove 17 and the locking lugs 21, are secondary connections which have no or only a slight support function under normal operational loads to have. Only when the pressure rises above the normal operating pressure, in particular when the main connections 31, 32, 33 fail, do the secondary connections 34, 35 perform a supporting function.

The main connections 31, 32, 33 are in constant engagement and ensure the integrity of the implanted infusion pump under normal conditions. When the internal pressure increases either in the annular space 28 or in the medicament store 7, the secondary connections 34, 35 increasingly come into engagement. As a result, the voltages are derived from the main connections 31, 32, 33 and are divided between main and secondary connections.

If, for example, the main connection 31 fails, the connection task is taken over by the secondary connection 34. Since there is a gap between the upper chamber part 3 and the lower chamber part 2 at the same time, medication escapes into the annular space 28 between the union part 4 and the upper chamber part 3, so that pressure and thus the load on the connection as a whole also decrease. As a result, the secondary connection 34 is able to ensure the integrity of the infusion pump to the outside. It is essential that the lower part fails in the upper web area, but not in the lower area, which can be ensured by design.

If the main connection 32 between the chamber part 3 and the union part 4 fails, the connection is also taken over by the secondary connection 34.

Accordingly, if the main connection 33 fails or is overloaded, a takeover or distribution to the secondary connection 35 is transmitted.

In any case, there is the advantage that in the event of an overload or failure of the main connections 31, 32, 33 secondary connections 34, 35 are available which ensure the safe continued operation of the infusion pump 1, which considerably improves the safety for a patient.

• i) Polyethylenfolie, Dicke 70 µm
• ii) Aluminiumfolie, Dicke 12 µm
• iii) Polyethylentherphtalat-Folie, Dicke 12 µm.

The partition 6 used in this example corresponds to the partition 6 used in Example 1 both in terms of composition and shape. The aluminum composite foil P is curved by deep drawing the contour of the inner wall of the lower chamber part 2 and is connected to the partition 6 at the edges along the circumference. The aluminum composite film P has, as viewed from the pressure chamber 8, the following composition:

• i) polyethylene film, thickness 70 microns
• ii) aluminum foil, thickness 12 µm
• iii) Polyethylene terephthalate film, thickness 12 microns.

The pill-shaped pressure chamber 8 thus formed has an internal volume of approximately 40 ml and contains approximately 2 ml of the propellant. The medication store can hold about 30 ml of the medical solution. This infusion pump according to the invention allows up to a maximum of 120 fillings with the medical solution and delivery rates per day of e.g. 0.7, 1.0, 1.4 or 2 ml of the medical solution.

Claims (2)

Implantable infusion pump (1) for the metered delivery of medication into the human body, with a pump chamber which is formed by a lower chamber part (2) and an upper chamber part (3) connected to it, wherein a) the pump chamber is separated into two partial chambers by a gas-impermeable flexible partition (6), b) the first partial chamber is delimited by the upper chamber part (3) and the flexible partition (6) and is designed as a storage for medical solutions (7), the upper chamber part (3) has a refill opening (12) which is penetrated by at least one pierceable septum ( 13) is sealed, and the memory (7) for medical solutions is connected to an outlet catheter via an outlet opening and optionally an outlet reducing device, and c) the second partial chamber is delimited by the lower chamber part (2) and the flexible partition (6) and is designed as a pressure chamber (8) for receiving a blowing agent made of halogenated hydrocarbon, characterized,
that the blowing agent is hexafluorobutane. Infusion pump according to claim 1, characterized in that the propellant is 1,1,1,4,4,4-hexafluorobutane.

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